For the last 2 years we have compared the radioiodinated membrane proteins of mouse peritoneal macrophages induced by different immunomodulators. The results show that membrane profiles of all peritoneal macrophage populations share greater similarity with one another than with other lymphoid cells. Within the limited series studies, macrophage populations can be classified into three subclasses: (1) nontumoricidal; (2) inflammatory; and (3) tumoricidal macrophages induced by bacterial adjuvants or pyran copolymer. Three proteins are present at much higher relative amounts in thioglycollate-broth-primed macrophages. The immediate goal is to determine whether these macrophage proteins are membrane ectoenzymes by labeling the macrophages with active site specific irreversible inhibitors. In comparing macrophage membrane proteins with other lymphoid cells, we identified an 80-90,000 dalton glycoprotein band unique to macrophages to see if one or more components of this diffuse band correspond to the macrophage-"specific" antigen detected previously by rabbit antimouse macrophage serum. By analysis with 2-dimensional gel electrophoresis, we found that the band consists of a family of seven proteins with slightly different isoelectric focus points. In fact, the same proteins were identified on mouse neutrophils as well as rat peritoneal macrophages. An unsuccessful attempt was undertaken to generate xenoantisera against this family of proteins by immunizing rabbits with sections of the polyacrylamide gels containing these proteins. This failure could result from loss of antigenicity as a result of the biochemical manipulation or because the rabbits also express a similar set of proteins on their myeloid cells. In other words, this family of glycoprotein could be conserved in evolution, as suggested by their presence in both mice and rats.